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INTRODUCTION: Identifying novel treatment strategies for patients with ulcerative colitis (UC) and at risk of relapse is critical. The objective of this study was to assess the efficacy of beclomethasone dipropionate (BDP) in lowering fecal calprotectin (FC) levels in UC patients in clinical remission and at risk of relapse. METHODS: This multicenter study comprised a double-blind, randomized, placebo-controlled phase (part I) and an open-label, non-randomized phase (part II). Eligible participants with UC in clinical remission, treated with 5-aminosalicylic acid and with FC levels ≥250 µg/g were randomized to receive 5 mg/day of BDP or placebo for 4 weeks (part I). At week 5, patients with FC ≥100 µg/g were treated with 5 mg/day of BDP for 4 weeks (part II), and FC levels were tested at week 9. RESULTS: Forty-three patients were randomized: 22 received BDP (group A) and 21 placebo (group B). At week 4, 13 patients (59.1%) in group A and 3 (17.6%) in group B had FC levels <100 µg/g (p-value = 0.010). In the double-blind phase of the study, no patient relapsed in group A and 4 in group B (p-value = 0.049). Both treatment groups showed a favorable safety profile, with most common adverse events being gastrointestinal disorders. CONCLUSION: In this multicenter, randomized clinical trial including patients with UC in clinical remission but with elevated FC, BDP was efficacious in reducing FC and well-tolerated.
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Over the past decade, there has been an increase in accelerated drug development with successful regulatory approval that has provided rapid access of novel medicines to patients world-wide. This has created the opportunity for the pharmaceutical industry to continuously improve the process of quickly bringing new medicines to patients with unmet medical needs. This can be accomplished through sharing the learnings and advancements in drug development, enhancing regulatory interactions, and collaborating with academics on developing the underlying science to reduce drug development timelines. In this paper, the IQ Consortium - Accelerated Drug Development working group members intend to share recommendations for optimizing strategies that build efficiencies in accelerated pathways for regulatory approval. Information was obtained by surveying member pharmaceutical companies with respect to recent expedited submissions within the past 5 years to gain insights as to which development strategies were successful. The learnings from this analysis are provided, which includes shared learnings in formulation development, stability, analytical methods, manufacturing, and importation testing as well as regulatory considerations. Each of these sections provide a summary illustrating the key data collected as well as a discussion that is aimed to guide pharmaceutical companies on strategies to consider streamlining development activities and expedite the drug to market.
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Desarrollo de Medicamentos , Industria Farmacéutica , Industria Farmacéutica/métodos , Desarrollo de Medicamentos/métodos , Humanos , Aprobación de Drogas/métodos , Encuestas y Cuestionarios , Preparaciones Farmacéuticas/químicaRESUMEN
The mechanism of loss of propylparaben potency from formulations when in contact with polyvinyl chloride has been determined. It is caused by the adsorption of propylparaben onto polyvinyl chloride surfaces. The adsorption kinetics is best described using a pseudo-second order model based on non-linear fit. The rate of adsorption increases with increasing bulk concentration of propylparaben. Adsorption equilibrium isotherm was fitted to three isotherm models: Langmuir, Freundlich, and Temkin, using non-linear fit. The Freundlich and Temkin models show the best fit, indicating a multi-layer adsorption. Using this case study, we present a methodology to provide mechanistic insights into the compatibility data between pharmaceutical ingredients and product contact materials when sorption is involved.
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Parabenos , Cloruro de Polivinilo , Cloruro de Polivinilo/química , Parabenos/química , Adsorción , Cinética , Modelos QuímicosRESUMEN
The treatment of inflammatory bowel disease has undergone a significant transformation following the introduction of biologic drugs. Thanks to these drugs, treatment goals have evolved from clinical response and remission to more ambitious objectives, such as endoscopic or radiologic remission. However, even though biologics are highly effective, a significant percentage of patients will not achieve an initial response or may lose it over time. We know that there is a direct relationship between the trough concentrations of the biologic and its therapeutic efficacy, with more demanding therapeutic goals requiring higher drug levels, and inadequate exposure being common. Therapeutic drug monitoring of biologic medications, along with pharmacokinetic models, provides us with the possibility of offering a personalized approach to treatment for patients with IBD. Over the past few years, relevant information has accumulated regarding its utility during or after induction, as well as in the maintenance of biologic treatment, in reactive or proactive strategies, and prior to withdrawal or treatment de-escalation. The aim of this document is to establish recommendations regarding the utility of therapeutic drug monitoring of biologics in patients with inflammatory bowel disease, in different clinical practice scenarios, and to identify areas where its utility is evident, promising, or controversial.
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Productos Biológicos , Colitis Ulcerosa , Enfermedad de Crohn , Monitoreo de Drogas , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Productos Biológicos/farmacocinética , Enfermedades Inflamatorias del Intestino/tratamiento farmacológicoRESUMEN
PRCIS: Corneal hysteresis (CH) and pulsatile ocular blood volume (POBV) were significantly lower in the eye with greater damage in asymmetric glaucoma, without a difference in intraocular pressure (IOP) or central corneal thickness (CCT), and no difference in elastic parameters. OBJECTIVE: To compare biomechanical and vascular metrics between the eyes of patients with asymmetric glaucoma (ASYMM) and those with symmetric glaucoma (SYMM). PATIENTS AND METHODS: Forty-five patients were prospectively recruited and divided into ASYMM, defined as cup-to-disc (C/D) ratio difference >0.1 between eyes and SYMM, with C/D difference ≤0.1. For ASYMM, the smaller C/D was defined as the best eye ("best") and the fellow eye was defined as the worst eye ("worse"). All metrics were subtracted as "worse" minus "best," including the viscoelastic parameter CH, and elastic parameters from the Corvis ST, including stiffness parameter at first applanation, stiffness parameter at highest concavity, integrated inverse radius, deformation amplitude ratio, IOP, CCT, mean deviation (MD), ganglion cell complex (GCC), and POBV were included. Paired t tests were performed between eyes in both groups. Statistical analyses were performed with SAS using a significance threshold of P <0.05. RESULTS: For ASYMM (16 patients), "worse" showed significantly lower CH (-0.76 ± 1.22), POBV (-0.38 ± 0.305), MD (-3.66 ± 6.55), and GCC (-7.9 ± 12.2) compared with "best." No other parameters were significantly different. For SYMM (29 patients), there were no significantly different metrics between eyes. CONCLUSIONS: Lower CH, POBV, GCC, and worse MD were associated with greater glaucomatous damage in asymmetric glaucoma without a difference in IOP or CCT. Lower CH and GCC are consistent with previous studies. POBV, a new clinical parameter that may indicate reduced blood flow, is also associated with greater damage.
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Córnea , Presión Intraocular , Tonometría Ocular , Campos Visuales , Humanos , Presión Intraocular/fisiología , Femenino , Masculino , Estudios Prospectivos , Persona de Mediana Edad , Fenómenos Biomecánicos , Córnea/fisiopatología , Anciano , Campos Visuales/fisiología , Células Ganglionares de la Retina/patología , Elasticidad/fisiología , Disco Óptico/irrigación sanguínea , Glaucoma de Ángulo Abierto/fisiopatología , Glaucoma de Ángulo Abierto/diagnóstico , Glaucoma/fisiopatología , Fibras Nerviosas/patología , Enfermedades del Nervio Óptico/fisiopatología , Enfermedades del Nervio Óptico/diagnósticoRESUMEN
BACKGROUND: Crohn's disease (CD) is characterized by the development of complications over the course of the disease. It is crucial to identify predictive factors of disabling disease, in order to target patients for early intervention. We evaluated risk factors of disabling CD and developed a prognostic model. METHODS: In total, 511 CD patients were retrospectively analyzed. Univariate and multivariate logistic regression analyses were used to identify demographic, clinical, and biological risk factors. A predictive nomogram model was developed in a subgroup of patients with noncomplicated CD (inflammatory pattern and no perianal disease). RESULTS: The rate of disabling CD within 5 years after diagnosis was 74.6%. Disabling disease was associated with gender, location of disease, requirement of steroids for the first flare, and perianal lesions. In the subgroup of patients (310) with noncomplicated CD, the rate of disabling CD was 80%. In the multivariate analysis age at onset <40 years (OR = 3.46, 95% confidence interval [CI] = 1.52-7.90), extensive disease (L3/L4) (OR = 2.67, 95% CI = 1.18-6.06), smoking habit (OR = 2.09, 95% CI = 1.03-4.27), requirement of steroids at the first flare (OR = 2.20, 95% CI = 1.09-4.45), and albumin (OR = 0.59, 95% CI = 0.36-0.96) were associated with development of disabling disease. The developed predictive nomogram based on these factors presented good discrimination, with an area under the receiver operating characteristic curve of 0.723 (95% CI: 0.670-0.830). CONCLUSION: We identified predictive factors of disabling CD and developed an easy-to-use prognostic model that may be used in clinical practice to help identify patients at high risk and address treatment effectively.
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Enfermedad de Crohn , Humanos , Adulto , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/epidemiología , Enfermedad de Crohn/complicaciones , Estudios Retrospectivos , Reglas de Decisión Clínica , Factores de Riesgo , Esteroides/uso terapéutico , Toma de DecisionesRESUMEN
Pediatric high-grade gliomas (pHGGs) are diffuse and highly aggressive CNS tumors which remain incurable, with a 5-year overall survival of less than 20%. Within glioma, mutations in the genes encoding the histones H3.1 and H3.3 have been discovered to be age-restricted and specific of pHGGs. This work focuses on the study of pHGGs harboring the H3.3-G34R mutation. H3.3-G34R tumors represent the 9-15% of pHGGs, are restricted to the cerebral hemispheres, and are found predominantly in the adolescent population (median 15.0 years). We have utilized a genetically engineered immunocompetent mouse model for this subtype of pHGG generated via the Sleeping Beauty-transposon system. The analysis of H3.3-G34R genetically engineered brain tumors by RNA-Sequencing and ChIP-Sequencing revealed alterations in the molecular landscape associated to H3.3-G34R expression. In particular, the expression of H3.3-G34R modifies the histone marks deposited at the regulatory elements of genes belonging to the JAK/STAT pathway, leading to an increased activation of this pathway. This histone G34R-mediated epigenetic modifications lead to changes in the tumor immune microenvironment of these tumors, towards an immune-permissive phenotype, making these gliomas susceptible to TK/Flt3L immune-stimulatory gene therapy. The application of this therapeutic approach increased median survival of H3.3-G34R tumor bearing animals, while stimulating the development of anti-tumor immune response and immunological memory. Our data suggests that the proposed immune-mediated gene therapy has potential for clinical translation for the treatment of patients harboring H3.3-G34R high grade gliomas.
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Neutralizing antibodies (NAs) are key immunological markers and are part of the humoral response of the adaptive immune system. NA assays determine the presence of functional antibodies to prevent SARS-CoV-2 infection. We performed a real-world evidence study to detect NAs that confer protection against SARS-CoV-2 after the application of five vaccines (Pfizer/BioNTech, AstraZeneca, Sinovac, Moderna, and CanSino) in the Mexican population. Side effects of COVID-19 vaccines and clinical and demographic factors associated with low immunogenicity were also evaluated. A total of 242 SARS-CoV-2-vaccinated subjects were recruited. Pfizer/BioNTech and Moderna proved the highest percentage of inhibition in a mono-vaccine scheme. Muscular pain, headache, and fatigue were the most common adverse events. None of the patients reported severe adverse events. We found an estimated contagion-free time of 207 (IQR: 182-231) and 187 (IQR: 184-189) days for Pfizer/BioNTech and CanSino in 12 cases in each group. On the basis of our results, we consider that the emerging vaccination strategy in Mexico is effective and safe.
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Hereditary cancer syndromes (HCS) are genetic diseases with an increased risk of developing cancer. This research describes the implementation of a cancer prevention model, genetic counseling, and germline variants testing in an oncologic center in Mexico. A total of 315 patients received genetic counseling, genetic testing was offered, and 205 individuals were tested for HCS. In 6 years, 131 (63.90%) probands and 74 (36.09%) relatives were tested. Among the probands, we found that 85 (63.9%) had at least one germline variant. We identified founder mutations in BRCA1 and a novel variant in APC that led to the creation of an in-house detection process for the whole family. The most frequent syndrome was hereditary breast and ovarian cancer syndrome (HBOC) (41 cases with BRCA1 germline variants in most of the cases), followed by eight cases of hereditary non-polyposic cancer syndrome (HNPCC or Lynch syndrome) (with MLH1 as the primarily responsible gene), and other high cancer risk syndromes. Genetic counseling in HCS is still a global challenge. Multigene panels are an essential tool to detect the variants frequency. Our program has a high detection rate of probands with HCS and pathogenic variants (40%), compared with other reports that detect 10% in other populations.
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Pruebas Genéticas , Síndromes Neoplásicos Hereditarios , Femenino , Humanos , México , Síndromes Neoplásicos Hereditarios/genética , Mutación de Línea Germinal , Células GerminativasRESUMEN
Prolactin (PRL) is a hormone expressed in lactotrophs cells of the pituitary gland in primates. Extra pituitary expression of PRL has been reported, including the eye; however, expression in the developing eye of primates is limited. The aim of the study was determining the expression of PRL and PRL receptor (PRLR) (mRNAs and proteins) in adult and fetal baboon (Papio hamadryas) ocular tissues. METHODS: We analyzed PRL and PRLR in baboon eyes tissues by immunofluorescence. The mRNAs of PRL and PRLR were detected by RT-PCR, cDNA was cloned, and sequenced. Furthermore, we performed a phylogenetic analysis to identify the evolutionary forces that underlie the divergence of PRL and PRLR primate genes. RESULTS: We observed the expression of PRL and PRLR (mRNAs and proteins) in all retinal cell lineages of fetal and adult baboon. PRL and PRLR fit the hypothesis of evolutionary purifying gene selection. CONCLUSIONS: mRNA and protein of PRL and PRLR are expressed in fetal and adult baboon retinal tissue. PRL may trigger autocrine and paracrine-specific actions in retinal cell lines.
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Pediatric high-grade gliomas (pHGGs) are the leading cause of cancer-related deaths in children in the USA. Sixteen percent of hemispheric pediatric and young adult HGGs encode Gly34Arg/Val substitutions in the histone H3.3 (H3.3-G34R/V). The mechanisms by which H3.3-G34R/V drive malignancy and therapeutic resistance in pHGGs remain unknown. Using a syngeneic, genetically engineered mouse model (GEMM) and human pHGG cells encoding H3.3-G34R, we demonstrate that this mutation led to the downregulation of DNA repair pathways. This resulted in enhanced susceptibility to DNA damage and inhibition of the DNA damage response (DDR). We demonstrate that genetic instability resulting from improper DNA repair in G34R-mutant pHGG led to the accumulation of extrachromosomal DNA, which activated the cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway, inducing the release of immune-stimulatory cytokines. We treated H3.3-G34R pHGG-bearing mice with a combination of radiotherapy (RT) and DNA damage response inhibitors (DDRi) (i.e., the blood-brain barrier-permeable PARP inhibitor pamiparib and the cell-cycle checkpoint CHK1/2 inhibitor AZD7762), and these combinations resulted in long-term survival for approximately 50% of the mice. Moreover, the addition of a STING agonist (diABZl) enhanced the therapeutic efficacy of these treatments. Long-term survivors developed immunological memory, preventing pHGG growth upon rechallenge. These results demonstrate that DDRi and STING agonists in combination with RT induced immune-mediated therapeutic efficacy in G34-mutant pHGG.
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Neoplasias Encefálicas , Citocinas , Reparación del ADN , Glioma , Histonas , Proteínas de la Membrana , Nucleotidiltransferasas , Animales , Niño , Humanos , Ratones , Adulto Joven , Neoplasias Encefálicas/genética , Reparación del ADN/efectos de los fármacos , Reparación del ADN/genética , Glioma/genética , Histonas/genética , Inmunidad , Mutación , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Citocinas/inmunología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéuticoRESUMEN
An early detection tool for latent COVID-19 infections in oncology staff and patients is essential to prevent outbreaks in a cancer center. (1) Background: In this study, we developed and implemented two early detection tools for the radiotherapy area to identify COVID-19 cases opportunely. (2) Methods: Staff and patients answered a questionnaire (electronic and paper surveys, respectively) with clinical and epidemiological information. The data were collected through two online survey tools: Real-Time Tracking (R-Track) and Summary of Factors (S-Facts). Cut-off values were established according to the algorithm models. SARS-CoV-2 qRT-PCR tests confirmed the positive algorithms individuals. (3) Results: Oncology staff members (n = 142) were tested, and 14% (n = 20) were positives for the R-Track algorithm; 75% (n = 15) were qRT-PCR positive. The S-Facts Algorithm identified 7.75% (n = 11) positive oncology staff members, and 81.82% (n = 9) were qRT-PCR positive. Oncology patients (n = 369) were evaluated, and 1.36% (n = 5) were positive for the Algorithm used. The five patients (100%) were confirmed by qRT-PCR. (4) Conclusions: The proposed early detection tools have proved to be a low-cost and efficient tool in a country where qRT-PCR tests and vaccines are insufficient for the population.
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Breast cancer (BC) has one of the highest incidences and mortality worldwide. Single nucleotide polymorphisms (SNPs) in TOX3 rs3803662 and MMP7 rs1943779 have been associated with susceptibility to BC. In this case-control study, we evaluated the association of rs3803662 (TOX3)/rs1943779 (MMP7) SNPs with clinical features, immunohistochemical reactivity, and risk association with BC in women from northeastern Mexico. We compared 212 BC cases and 212 controls. DNA was isolated from peripheral blood to perform the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. We calculated genotype frequencies, odds ratios, and 95% confidence intervals. We found that CT (Cytocine-Thymine) and TT (Thymine -Thymine) genotypes, and T alleles of TOX3 rs3803662, were associated with BC risk (p = 0.034, p = 0.011, respectively). SNP TOX3 rs3803662 was associated with positive progesterone receptors (PR) and triple-negative BC (TNBC) but not with estrogen receptor (ER) or HER2 reactivity. CT and TT genotypes (p = 0.006) and T alleles (p = 0.002) of SNP MMP7 rs1943779 were associated with risk of BC. We found that T alleles of TOX3 rs3803662 and MMP7 rs1943779 SNPs are associated with BC risk. These findings contribute to personalized medicine in Mexican women.
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Proteínas Reguladoras de la Apoptosis/genética , Neoplasias de la Mama , Transactivadores/genética , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Humanos , Metaloproteinasa 7 de la Matriz/genética , México , Polimorfismo de Nucleótido Simple/genética , Receptores de Progesterona/genéticaRESUMEN
BACKGROUND: Cardiac surgery with extracorporeal circulation (ECC) requires the administration of anticoagulant drugs to maintain ACT ranges 400-600 seconds, which requires exhaustive coagulation monitoring for which various point-of-care devices are available. However, there is variability between them, so we aimed to compare the values in ACT measurement. METHODS: Simultaneous ACT measurements were performed with the Hemochron Response®, Hemostasis Management System Plus® (HMS Plus®) and Hemochron Signature® systems. RESULTS: A total of 255 simultaneous measurements were taken, the mean and standard deviation (SD) of each device were: Hemochron Signature® 361.1 seconds (SD: 156.9), HMS Plus® 412.8 seconds (SD: 180.9) and Hemochron Response® 422.8 seconds (SD: 187.9), being these differences statistically significant (Fridman's test p < 0.01). For comparisons the Bland-Altman method was used, resulting the Hemochron Response® has 61.7 seconds higher mean values than the Hemochron Signature®, the Hemochron Response® 10 seconds higher than the HMS Plus® and the HMS Plus® 51.7 seconds higher than the Hemochron Signature®. CONCLUSION: The differences found in comparisons are considered to be clinically relevant, which is why it is considered important to make the variability of the different monitoring systems known and to take them into account for optimal control of this parameter and its clinical repercussions.
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Procedimientos Quirúrgicos Cardíacos , Sistemas de Atención de Punto , Anticoagulantes , Pruebas de Coagulación Sanguínea , Heparina , Humanos , Tiempo de Coagulación de la Sangre TotalRESUMEN
We report the available evidence demonstrating the biosimilarity of ABP 501 (AMGEVITA®, adalimumab-atto) to its reference product (RP) (Humira®, adalimumab), and the rationale for the extrapolation of the results obtained with the RP in inflammatory bowel disease (IBD) to ABP 501. Based on its preclinical and clinical data, ABP 501 has been authorized for use in Europe in all the indications approved for the RP, including Crohn's disease and ulcerative colitis.
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Biosimilares Farmacéuticos , Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Adalimumab/uso terapéutico , Biosimilares Farmacéuticos/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológicoRESUMEN
Mutant isocitrate dehydrogenase 1 (IDH1-R132H; mIDH1) is a hallmark of adult gliomas. Lower grade mIDH1 gliomas are classified into 2 molecular subgroups: 1p/19q codeletion/TERT-promoter mutations or inactivating mutations in α-thalassemia/mental retardation syndrome X-linked (ATRX) and TP53. This work focuses on glioma subtypes harboring mIDH1, TP53, and ATRX inactivation. IDH1-R132H is a gain-of-function mutation that converts α-ketoglutarate into 2-hydroxyglutarate (D-2HG). The role of D-2HG within the tumor microenvironment of mIDH1/mATRX/mTP53 gliomas remains unexplored. Inhibition of D-2HG, when used as monotherapy or in combination with radiation and temozolomide (IR/TMZ), led to increased median survival (MS) of mIDH1 glioma-bearing mice. Also, D-2HG inhibition elicited anti-mIDH1 glioma immunological memory. In response to D-2HG inhibition, PD-L1 expression levels on mIDH1-glioma cells increased to similar levels as observed in WT-IDH gliomas. Thus, we combined D-2HG inhibition/IR/TMZ with anti-PDL1 immune checkpoint blockade and observed complete tumor regression in 60% of mIDH1 glioma-bearing mice. This combination strategy reduced T cell exhaustion and favored the generation of memory CD8+ T cells. Our findings demonstrate that metabolic reprogramming elicits anti-mIDH1 glioma immunity, leading to increased MS and immunological memory. Our preclinical data support the testing of IDH-R132H inhibitors in combination with IR/TMZ and anti-PDL1 as targeted therapy for mIDH1/mATRX/mTP53 glioma patients.
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Reprogramación Celular , Glioma/terapia , Glutaratos/farmacología , Animales , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Línea Celular Tumoral , Reprogramación Celular/efectos de los fármacos , Reprogramación Celular/genética , Reprogramación Celular/inmunología , Quimioradioterapia , Mutación con Ganancia de Función , Glioma/genética , Glioma/inmunología , Glioma/patología , Humanos , Memoria Inmunológica/efectos de los fármacos , Memoria Inmunológica/genética , Isocitrato Deshidrogenasa/genética , Isocitrato Deshidrogenasa/inmunología , Ratones , Temozolomida/farmacología , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/inmunología , Proteína Nuclear Ligada al Cromosoma X/genética , Proteína Nuclear Ligada al Cromosoma X/inmunologíaRESUMEN
INTRODUCTION: there is a rising number of patients receiving antiplatelet and anticoagulation therapy who require endoscopic retrograde cholangiopancreatography (ERCP), probably due to the increased morbidity of older patients. Considering the increasing use of direct oral anticoagulants (DOACs), this study aimed to determine the influence of these factors on the possibility of hemorrhage after ERCP in our center. MATERIAL AND METHODS: data were collected from all the examinations carried out in 2017 and 2018, which included 797 examinations on 588 patients. Collected data included personal history of the patients, results of the test and follow-up. RESULTS: the percentage of post-ERCP bleeding was 4.6 % (n = 37). With regard to the severity, the bleeding was mild in 21.6 % (n = 8) of the cases, moderate in 59.5 % (n = 22) and severe in 18.9 % (n = 7). Previous cardiopathy antiplatelet therapy, anticoagulation therapy, treatment with DOACs, having a pancreatic stent and lithiasis removal doubled the risk of bleeding after ERCP. Having a sphincterotomy increased the risk by over five-fold. CONCLUSION: according to the multivariate analysis, a statistically significant increase of bleeding among patients treated with DOACs was observed compared to patients who received anticoagulation with acenocoumarol or low-molecular-weight heparins (LMWH).
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Colangiopancreatografia Retrógrada Endoscópica , Heparina de Bajo-Peso-Molecular , Anticoagulantes/efectos adversos , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Hemorragia , Humanos , Estudios Retrospectivos , Factores de Riesgo , StentsRESUMEN
Brainstem gliomas are aggressive tumors that are more prevalent in pediatric patients. The location of these tumors makes them inoperable, and currently there is no effective treatment. Recent genomic data revealed the unique biology of these tumors. The following protocol provides a method to incorporate these specific genetic lesions in a mouse glioma model. Using this model, the effects of these mutations in tumor progression and response to treatments can be studied within a relevant in vivo context. For complete details on the use and execution of this protocol, please refer to Mendez et al. (2020).